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https://doi.org/10.1590/0004-282X20170138
HISTORICAL NOTE
Mary Broadfoot Walker: 83 years since a
historical discovery
Mary Broadfoot Walker: 83 anos desde uma descoberta histórica
Vitor Martinez de Carvalho1, Eduardo de Almeida Guimarães Nogueira1, Gleysson Rodrigues Rosa2, Yara
Dadalti Fragoso1
1Universidade Metropolitana de Santos, Departamento de Neurologia, Santos SP, Brasil.
2Harvard Medical School, Spaulding Rehabilitation Hospital, Department of Physical Medicine and Rehabilitation, Charlestown, MA USA.
Correspondence: Yara Dadalti Fragoso; Departamento de Neurologia da Faculdade de Medicina da UNIMES; Avenida Conselheiro Nebias, 536; 11045-002 Santos SP, Brasil; E-mail: yara@bsnet.com.br
Conflict of interest: There is no conflict of interest to declare.
Received 13 June 2017; Received in final form 01 August 2017; Accepted 05 August 2017.
ABSTRACT
Mary Broadfoot Walker was a Scottish physician who, in 1935, described in great detail the effect of an anticholinesterase drug (physostigmine) on the signs and symptoms of myasthenia gravis. An original five-minutes movie is available online and the skepticism of her contemporary British medical doctors is understandable when the drastic effect of the treatment is shown in this movie. What Mary Walker taught us, more than eight decades ago, about myasthenia gravis continues to be the basis of a pharmacological diagnostic test and treatment of this disease.
Keywords: myasthenia gravis; physostigmine; neostigmine; acetylcholinesterase.
RESUMO
Mary Broadfoot Walker foi uma médica escocesa que em 1935 descreveu em grande detalhe o efeito de uma droga anticolinesterásica (fisostigmina) nos sinais e sintomas da myasthenia gravis. Um filme original com cinco minutos de duração está disponível online e a reação cética dos colegas médicos contemporâneos de Mary é compreensível dado o drástico efeito terapêutico mostrado neste filme. O que Mary Walker nos ensinou mais de oito décadas atrás continua a ser a base de um teste diagnóstico farmacológico e do tratamento da myasthenia gravis.
Palavras-chave: miastenia gravis; fisostigmina; neostigmina; acetilcolinesterase.
Mary Broadfoot Walker was born in Croft-an-Righ, Wigtown, Scotland, and graduated from the Medical College of Glasgow and Edinburgh in 1913. She overcame the preju-dices of that era and the barriers imposed by society. During World War I, she joined the Royal Army Medical Corps and
served at the 63rd General Hospital in Malta. After the war,
in 1920, she became Assistant Medical Oicer in ‘Poor Law
Service’ at St. Alfege’s Hospital in Greenwich. Over the years she became an academic, a doctor and a scientist and, against formidable competition in 1932, she passed the test for
London Membership of the Royal College of Physicians. Her
name is forever associated with the “Miracle of Saint Alfege’s
Hospital”, that is, the efect of administration of physostig -mine to patients with myasthenia gravis. Mary Walker’s clini-cal awareness and her clini-calm but determined manner paved the way to the understanding and treatment of this disease,
with an inluence that extends to the present day.
Physostigmine is a highly toxic parasympathomimetic alkaloid extracted from the Calabar bean, which is indigenous
to western Africa. It acts as a potent antagonist of atropine
through a reversible anticholinesterase reaction. In 1876,
Harnack demonstrated the efect of physostigmine for boost
-ing the electrical stimulation of mammalian striated muscle1.
Sixty-two years later, Mary Walker described and showed two
cases of very severe myasthenia gravisthat were drastically
improved through administration of physostigmine and, later on, prostigmin. Although prostigmin (neostigmine) was bet-ter tolerated by the patients, Mary highlighted that the price
of nine pence per vial rendered it diicult to use in daily prac
-tice. he presentation of the dramatic improvement of the
myasthenia patients took place at the clinical meeting of the Royal Society of Medicine (Neurology) at the National Hospital,
Queen Square, London, on 17 February 1938, and was pub
-lished in detail2,3. Mary concluded that myasthenia gravis was
the pathological efect of a substance that entered the circula -tion and caused abnormal fatigability via the acetylcholine in
the neuromuscular junction4. Mary’s observations were
826 Arq Neuropsiquiatr 2017;75(11):825-826
showing the efect of anticholinesterase agents on ptosis. he
demonstration of her innovative treatment was immortalized in a movie produced in 1935, which is accessible online5.
he “Mary Walker efect” was later described and the humoral aspect of muscle tiredness was highlighted. he patient vigorously exercised the forearm with a tourniquet
applied at the elbow. When the arm presented with muscle fatigue, the tourniquet was released and partial ptosis
devel-oped a few minutes later6. In addition, Mary was involved in
the description of familial periodic paralysis and hypokalemia7. Mary Walker’s papers and presentations at the Royal Society of Medicine were received with a degree of skepti-cism and led to great discussion among the specialists of that
era. he efect of this treatment was so dramatic and, at the
same time, so short-lived, that it resembled nothing previously
seen. he famous neurologist Denny-Brown, who earlier com
-pared curare poisoning to myasthenia gravis(and this was
how Mary thought of physostigmine as a potential treatment),
stood against Mary’s discoveries and explanations8. Others
supported her indings, but she never received a Fellowship of
the Royal College of Physicians and never occupied a teach
-ing hospital position9. She was awarded the Jean Hunter Prize
in 1962 “for the advancement of research into the treatment of
nervous exhaustion and for her original contribution to the fun-damental knowledge of the nature of myasthenia gravis, made while carrying out the routine duties of a medical oicer at a large metropolitan hospital” 8. Although it is now acknowledged
that a German physician may have been the irst to report on the efect of anticholinesterase agents in myasthenia gravis4, it was only through Mary B. Walker that the treatment became known, after detailed presentation of her results.
Mary retired to her native Scotland and died in compara-tive obscurity in Wigtown in 1974, at the advanced age of 86 years. She was surrounded by her cats and with neighbors who had the nicest words about the lady who had a walnut tree in her garden4,9,10.
Mary Broadfoot Walker was, perhaps, the only scientist
to have made history with a “n = 1” treatment. Later she pre
-sented the second case, and “n = 2” was suicient to convince
others to try this therapy.
A
B
Figure. (A) Photo of Mary B. Walker; (1888-1974) (B) photo from her Letter to The Lancet in 1934, reporting on the dramatic effect of physostigmine on a patient with myasthenia gravis.
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4. Croitoru C, Turliuc D, Danciu F, Cucu A, Costea C. The miracle of St. Alfege’s Hospital and the history of the treatment of myasthenia gravis. Rom Neurosurg. 2017;1:73-9. https://doi.org/10.1515/romneu-2017-0011 5. 1935 Prostigmin demonstration for MG. 2007 [cited 2017 Aug 1].
Available from: https://www.youtube.com/watch?v=uRoRsmvkhTI
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